{"id":"13e3e006-9064-5d52-a36d-8731113ac0a6","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-lysosome-bile-export","predicate":"promotes","statement":"Stimulating lysosomal exocytosis increased ATP7B delivery toward the canalicular membrane and copper release into the biliary space.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"20b99337-f783-5dc3-a97c-b0b525bd5a50","mechanism_event_label":"Lysosome fusion provides a route out of the liver cell for excess copper.","subject":{"id":"5161f019-6c44-5d5b-bb95-9405c28fad39","slug":"apical-lysosomal-exocytosis","display_name":"Lysosomal exocytosis at the hepatocyte canalicular pole","entity_type_key":"cellular_process"},"object":{"id":"abb6f6bd-6ec9-56e4-96df-e8bb3eb9b97c","slug":"biliary-copper-export","display_name":"Copper excretion toward bile","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"20b99337-f783-5dc3-a97c-b0b525bd5a50","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-lysosome-bile-export-event","event_type":"biochemical_relationship","label":"Lysosome fusion provides a route out of the liver cell for excess copper.","description":"Stimulating lysosomal exocytosis increased ATP7B delivery toward the canalicular membrane and copper release into the biliary space.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"05dae672-bbd9-585d-8713-ccfe9e14d26a","slug":"atp7b","display_name":"Human copper-transporting ATPase ATP7B","entity_type_key":"protein"},"role":"copper transporter","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5161f019-6c44-5d5b-bb95-9405c28fad39","slug":"apical-lysosomal-exocytosis","display_name":"Lysosomal exocytosis at the hepatocyte canalicular pole","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"abb6f6bd-6ec9-56e4-96df-e8bb3eb9b97c","slug":"biliary-copper-export","display_name":"Copper excretion toward bile","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/copper-research/24909901.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b\", \"start_char\": 0, \"end_char\": 1036, \"text_sha256\": \"abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Copper perturbation, imaging and trafficking assays in hepatocyte systems","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Copper challenge and lysosomal exocytosis perturbation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The main cellular trafficking observations are mechanistic; experimental copper exposures and mutant rescue do not establish a clinical treatment. Dynactin p62 is DCTN4, not autophagy SQSTM1/p62.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Copper research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"copper","display_name":"Copper","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human HepG2 cells with complementary hepatic models","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Lysosome fusion provides a route out of the liver cell for excess copper.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[copper-p24909901] Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. 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Dynactin p62 is DCTN4, not autophagy SQSTM1/p62.\nexposure: Copper challenge and lysosomal exocytosis perturbation\nevidence_span: {\"source_cache\": \"artifacts/copper-research/24909901.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b\", \"start_char\": 0, \"end_char\": 1036, \"text_sha256\": \"abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b\"}\n[copper-p24909901] Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24909901/ DOI: 10.1016/j.devcel.2014.04.033","model_system":"Copper perturbation, imaging and trafficking assays in hepatocyte systems","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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